Background: and Purpose Symptomatic intracranial hemorrhage (sICH) following endovascular thrombectomy (EVT) is a severe complication associated with adverse functional outcomes and increased mortality rates. Currently, a reliable predictive model for sICH risk after EVT is lacking. Methods: This study used data from patients aged ≥20 years who underwent EVT for anterior circulation stroke from the nationwide Taiwan Registry of Endovascular Thrombectomy for Acute Ischemic Stroke (TREAT-AIS). A predictive model including factors associated with an increased risk of sICH after EVT was developed to differentiate between patients with and without sICH. This model was compared existing predictive models using nationwide registry data to evaluate its relative performance. Results: Of the 2,507 identified patients, 158 developed sICH after EVT. Factors such as diastolic blood pressure, Alberta Stroke Program Early CT Score, platelet count, glucose level, collateral score, and successful reperfusion were associated with the risk of sICH after EVT. The TREAT-AIS score demonstrated acceptable predictive accuracy (area under the curve [AUC]=0.694), with higher scores being associated with an increased risk of sICH (odds ratio=2.01 per score increase, 95% confidence interval=1.64–2.45, P<0.001). The discriminatory capacity of the score was similar in patients with symptom onset beyond 6 hours (AUC=0.705). Compared to existing models, the TREAT-AIS score consistently exhibited superior predictive accuracy, although this difference was marginal. Conclusions The TREAT-AIS score outperformed existing models, and demonstrated an acceptable discriminatory capacity for distinguishing patients according to sICH risk levels. However, the differences between models were only marginal. Further research incorporating periprocedural and postprocedural factors is required to improve the predictive accuracy.

Background: and Purpose Symptomatic intracranial hemorrhage (sICH) following endovascular thrombectomy (EVT) is a severe complication associated with adverse functional outcomes and increased mortality rates. Currently, a reliable predictive model for sICH risk after EVT is lacking. Methods: This study used data from patients aged ≥20 years who underwent EVT for anterior circulation stroke from the nationwide Taiwan Registry of Endovascular Thrombectomy for Acute Ischemic Stroke (TREAT-AIS). A predictive model including factors associated with an increased risk of sICH after EVT was developed to differentiate between patients with and without sICH. This model was compared existing predictive models using nationwide registry data to evaluate its relative performance. Results: Of the 2,507 identified patients, 158 developed sICH after EVT. Factors such as diastolic blood pressure, Alberta Stroke Program Early CT Score, platelet count, glucose level, collateral score, and successful reperfusion were associated with the risk of sICH after EVT. The TREAT-AIS score demonstrated acceptable predictive accuracy (area under the curve [AUC]=0.694), with higher scores being associated with an increased risk of sICH (odds ratio=2.01 per score increase, 95% confidence interval=1.64–2.45, P<0.001). The discriminatory capacity of the score was similar in patients with symptom onset beyond 6 hours (AUC=0.705). Compared to existing models, the TREAT-AIS score consistently exhibited superior predictive accuracy, although this difference was marginal. Conclusions The TREAT-AIS score outperformed existing models, and demonstrated an acceptable discriminatory capacity for distinguishing patients according to sICH risk levels. However, the differences between models were only marginal. Further research incorporating periprocedural and postprocedural factors is required to improve the predictive accuracy.

Background: and Purpose Symptomatic intracranial hemorrhage (sICH) following endovascular thrombectomy (EVT) is a severe complication associated with adverse functional outcomes and increased mortality rates. Currently, a reliable predictive model for sICH risk after EVT is lacking. Methods: This study used data from patients aged ≥20 years who underwent EVT for anterior circulation stroke from the nationwide Taiwan Registry of Endovascular Thrombectomy for Acute Ischemic Stroke (TREAT-AIS). A predictive model including factors associated with an increased risk of sICH after EVT was developed to differentiate between patients with and without sICH. This model was compared existing predictive models using nationwide registry data to evaluate its relative performance. Results: Of the 2,507 identified patients, 158 developed sICH after EVT. Factors such as diastolic blood pressure, Alberta Stroke Program Early CT Score, platelet count, glucose level, collateral score, and successful reperfusion were associated with the risk of sICH after EVT. The TREAT-AIS score demonstrated acceptable predictive accuracy (area under the curve [AUC]=0.694), with higher scores being associated with an increased risk of sICH (odds ratio=2.01 per score increase, 95% confidence interval=1.64–2.45, P<0.001). The discriminatory capacity of the score was similar in patients with symptom onset beyond 6 hours (AUC=0.705). Compared to existing models, the TREAT-AIS score consistently exhibited superior predictive accuracy, although this difference was marginal. Conclusions The TREAT-AIS score outperformed existing models, and demonstrated an acceptable discriminatory capacity for distinguishing patients according to sICH risk levels. However, the differences between models were only marginal. Further research incorporating periprocedural and postprocedural factors is required to improve the predictive accuracy.

Objective To investigate the effects of miR-4531/CX3CL1 signaling pathway on the vascular injury in preeclampsia, and to search possible targets for early diagnosis and prevention of preeclampsia. Methods Placental tissue samples were obtained from 10 patients with late-onset preeclampsia and 10 normal pregnant women in the Obstetrics and Gynecology Department of Minhang Hospital, Fudan University from October 2021 to December 2022. The levels of miR-4531 and CX3CL1 were evaluated by qRT-PCR. Cell transfection was performed by lipofectamine 2000 in vitro. The binding relationship between miR-4531 and CX3CL1 was determined by luciferase reporter assay. The apoptosis of neutrophils, the migration, repair, colony formation and cell-free DNA (cfDNA) release of human umbilical vein endothelial cells (HUVECs) were detected. Results MiR-4531 was significantly downregulated, and CX3CL1 was upregulated in placental tissues of preeclampsia patients (P＜0.05). Luciferase report assay confirmed the direct binding relationship between miR-4531 and CX3CL1. Upregulation of miR-4531significantly promoted the migration, proliferation, repair, and inhibited cfDNA release of HUVECs and neutrophils apoptosis in medium under hypoxic condition (P＜0.05). However, downregulation of miR-4531 obviously inhibited the proliferation, migration, repair, and enhanced cfDNA release of HUVECs and neutrophils apoptosis in medium under hypoxic condition (P＜0.05). Conclusions The miR-4531is downregulated in placental tissues of preeclampsia parients and is a potential therapeutic target for preeclampsia. It might cause endothelial damage and an abnormal hypercoagulable state under hypoxic condition by targeting and regulating the CX3CL1 pathway.

Objective To construct reference ranges of cardiac size and morphologic parameters in low-risk fetuses at 28-39 gestational weeks using two-dimensional speckle tracking technique.Methods A prospective collection of 453 low-risk singleton pregnancies with echocardiography at Obstetrics and Gynecology Hospital,Fudan University was used to assess the size(length,width,and area)and morphology(sphericity index,i.e.,the ratio of length to width)of the fetal four-chamber view and two ventricles using two-dimensional speckle tracking technique.Repeated inter-and intra-observer agreement of measurements was assessed using the intraclass correlation coefficients(ICCs).Statistical analysis of cardiac measurement parameters was performed to establish reference ranges of values for cardiac size and morphology in low-risk fetuses.Results The inter-and intra-group ICCs for reproducibility tests of fetal cardiac parameters measurements were 0.691 to 0.980.Fetal four-chamber view and ventricular size increased with gestational week(all P<0.001),the end-diastolic length of the left ventricle was larger than that of the right ventricle,and the end-diastolic diameter was smaller than that of the right ventricle(both P<0.001),while there was no significant difference in the end-diastolic area of the two ventricles(P= 0.050).The spherical index of four-chamber view did not correlate with gestational week(P=0.811).The sphericity index of the basal and intermediate segments of the left ventricle was greater than that of the right ventricle,and the sphericity index of the apical segment was less than that of the right ventricle,the differences were statistically significant(all P<0.01).Conclusion The two-dimensional speckle tracking technique for measuring fetal cardiac parameters has good reproducibility.The reference ranges for cardiac size and morphology in low-risk fetuses developed in this study will be useful for prenatal evaluation of cardiac remodeling.

BACKGROUND:Kidney deficiency and blood stasis syndrome are common traditional Chinese medicine syndromes observed in knee osteoarthritis,which serve as fundamental pathogenesis factors.There exists a significant connection between the two.Previous studies have demonstrated that kidney deficiency and blood stasis syndrome effectively contribute to knee joint cartilage degeneration and the progression of knee osteoarthritis.However,the mechanisms underlying the promotion of knee joint cartilage damage remain unclear and require further investigation. OBJECTIVE:To investigate the influence of kidney deficiency and blood stasis syndrome on the progression of knee osteoarthritis in Sprague-Dawley rats. METHODS:Sixteen Sprague-Dawley rats were randomly divided into two groups:a model observation group and a control group,with eight rats in each group.Animal models of kidney deficiency were induced by ovary removal in the model observation group,while the control group was given a sham procedure for ovarian removal.Two months after modeling,both groups underwent modified HULTH surgery to induce knee osteoarthritis.One week after modified HULTH surgery,the model observation group was subcutaneously given adrenaline hydrochloride to make blood stasis models,while the control group was subcutaneously given normal saline.At the 5th week after modified HULTH surgery,blood rheology,coagulation parameters,triiodothyronine,tetraiodothyronine,and estradiol levels were measured.Knee joint X-ray images were taken,and knee joint sections were stained with safranin O-fast green,hematoxylin-eosin,and immunohistochemistry. RESULTS AND CONCLUSION:Compared with the control group,the model observation group exhibited significant increases in whole blood viscosity at low,medium,and high shear rates,as well as increased plasma viscosity.Fibronectin levels in the coagulation parameters were significantly increased,while prothrombin time and activated partial thromboplastin time were significantly decreased.Triiodothyronine,tetraiodothyronine,and estradiol levels were all significantly decreased.Radiographic results showed that the model observation group exhibited more severe degree of knee joint space narrowing and surface roughness,with the appearance of high-density shadows.Hematoxylin-eosin and safranin O-fast green staining demonstrated more severe cartilage damage in the model observation group,with significantly higher OARSI and Mankin scores compared with the control group.Compared with the control group,immunohistochemistry results showed a significant reduction in the expression of extracellular matrix type II collagen and aggrecan protein in the cartilage of the model observation group rats.Moreover,there was a significant increase in the expression of matrix metalloproteinase 13 and aggrecanase 5,which are inflammatory factors.These results indicate that the Sprague-Dawley rat model of knee osteoarthritis with kidney deficiency and blood stasis was successfully established.Kidney deficiency and blood stasis syndrome further aggravate cartilage extracellular matrix degradation and cartilage degeneration by promoting the expression of inflammatory factors,thereby promoting the progression of knee osteoarthritis in rats.

Osteoporotic proximal humeral fracture (OPHF) is one of the common osteoporotic fractures in the aged, with an incidence only lower than vertebral compression fracture, hip fracture, and distal radius fracture. OPHF, secondary to osteoporosis and characterized by poor bone quality, comminuted fracture pattern, slow healing, and severely impaired shoulder joint function, poses a big challenge to the current clinical diagnosis and treatment. In the field of diagnosis, treatment, and rehabilitation of OPHF, traditional Chinese and Western medicine have accumulated rich experience and evidence from evidence-based medicine and achieved favorable outcomes. However, there is still a lack of guidance from a relevant consensus as to how to integrate the advantages of the two medical systems and achieve the integrated diagnosis and treatment. To promote the diagnosis and treatment of OPHF with integrated traditional Chinese and Western medicine, relevant experts from Orthopedic Expert Committee of Geriatric Branch of Chinese Association of Gerontology and Geriatrics, Youth Osteoporosis Group of Orthopedic Branch of Chinese Medical Association, Osteoporosis Group of Orthopedic Surgeon Branch of Chinese Medical Doctor Association, and Osteoporosis Committee of Shanghai Association of Integrated Traditional Chinese and Western Medicine have been organized to formulate Expert consensus on the diagnosis and treatment of osteoporotic proximal humeral fracture with integrated traditional Chinese and Western medicine ( version 2024) by searching related literatures and based on the evidences from evidence-based medicine. This consensus consists of 13 recommendations about the diagnosis, treatment and rehabilitation of OPHF with integrated traditional Chinese medicine and Western medicine, aimed at standardizing, systematizing, and personalizing the diagnosis and treatment of OPHF with integrated traditional Chinse and Western medicine to improve the patients ′ function.

Objective To explore the targets and pathways of Cynanchum wilfordii for treatment of ulcerative colitis(UC).Methods UPLC-QE-MS was used to identify the components of Cynanchum wilfordii ethanol extract,and their targets were screened using public databases for construction of the core protein-protein interaction(PPI)network and GO and KEGG enrichment analyses.Forty male C57 mice were randomized into normal control group,model group,mesalazine group and Cynanchum wilfordii group(n=10),and in the latter 3 groups,mouse UC models were established by treatment with 2.5%DSS and the latter 2 groups drug interventions by gavage.The therapeutic effect was evaluated by recording body weight changes and DAI score.Pathological changes of the colon tissue were observed with HE and AB-PAS staining,and JAK2 and STAT3 protein expressions were detected with Western blotting.The metabolites and metabolic pathways were identified by metabonomics analysis.Results We identified 240 chemical components in Cynanchum wilfordii alcoholic extracts,including 19 steroids.A total of 177 Cynanchum wilfordii targets,5406 UC genes,and 117 intersection genes were obtained.JAK2 and STAT3 were the core targets and significantly enriched in lipid and atherosclerosis pathways.Cynanchum wilfordii treatment significantly increased the body weight and decreased DAI score of UC mice(P<0.05),alleviated intestinal pathologies,and decreased JAK2 and STAT3 protein expressions in the colon tissues.Most of the 83 intersecting differential metabolites between the control,model and Cynanchum wilfordii groups were identified as glycerophospholipids,arachidonic acid,and amino acids involving glycerophospholipid metabolism and other pathways.Correlation analysis suggested that the core targets of Cynanchum wilfordii for UC participated in regulation of the metabolites.Conclusion Cynanchum wilfordii alleviates lipid and amino acid metabolism disorders to lessen UC in mice by regulating the core targets including JAK2 and STAT3 and the levels of endogenous metabolites.

Background::Atopic dermatitis (AD) affects approximately 10% of adults worldwide. CM310 is a humanized monoclonal antibody targeting interleukin-4 receptor alpha that blocks interleukin-4 and interleukin-13 signaling. This trial aimed to evaluate the efficacy and safety of CM310 in Chinese adults with moderate-to-severe AD.Methods::This multicenter, randomized, double-blind, placebo-controlled, phase 2b trial was conducted in 21 medical institutions in China from February to November 2021. Totally 120 eligible patients were enrolled and randomized (1:1:1) to receive subcutaneous injections of 300 mg CM310, 150 mg CM310, or placebo every 2 weeks for 16 weeks, followed by an 8-week follow-up period. The primary endpoint was the proportion of patients achieving ≥75% improvement in the Eczema Area and Severity Index (EASI-75) score from baseline at week 16. Safety and pharmacodynamics were also studied.Results::At week 16, the proportion of EASI-75 responders from baseline was significantly higher in the CM310 groups (70% [28/40] for high-dose and 65% [26/40] for low-dose) than that in the placebo group (20%[8/40]). The differences in EASI-75 response rate were 50% (high vs. placebo, 95% CI 31%–69%) and 45% (low vs. placebo, 95% CI 26%–64%), with both P values <0.0001. CM310 at both doses also significantly improved the EASI score, Investigator’s Global Assessment score, daily peak pruritus Numerical Rating Scale, AD-affected body surface area, and Dermatology Life Quality Index compared with placebo. CM310 treatment reduced levels of thymus and activation-regulated chemokine, total immunoglobulin E, lactate dehydrogenase, and blood eosinophils. The incidence of treatment-emergent adverse events (TEAEs) was similar among all three groups, with the most common TEAEs reported being upper respiratory tract infection, atopic dermatitis, hyperlipidemia, and hyperuricemia. No severe adverse events were deemed to be attributed to CM310. Conclusion::CM310 at 150 mg and 300 mg every 2 weeks demonstrated significant efficacy and was well-tolerated in adults with moderate-to-severe AD.Trial Registration::ClinicalTrials.gov, NCT04805411.

Objective To explore the targets and pathways of Cynanchum wilfordii for treatment of ulcerative colitis(UC).Methods UPLC-QE-MS was used to identify the components of Cynanchum wilfordii ethanol extract,and their targets were screened using public databases for construction of the core protein-protein interaction(PPI)network and GO and KEGG enrichment analyses.Forty male C57 mice were randomized into normal control group,model group,mesalazine group and Cynanchum wilfordii group(n=10),and in the latter 3 groups,mouse UC models were established by treatment with 2.5%DSS and the latter 2 groups drug interventions by gavage.The therapeutic effect was evaluated by recording body weight changes and DAI score.Pathological changes of the colon tissue were observed with HE and AB-PAS staining,and JAK2 and STAT3 protein expressions were detected with Western blotting.The metabolites and metabolic pathways were identified by metabonomics analysis.Results We identified 240 chemical components in Cynanchum wilfordii alcoholic extracts,including 19 steroids.A total of 177 Cynanchum wilfordii targets,5406 UC genes,and 117 intersection genes were obtained.JAK2 and STAT3 were the core targets and significantly enriched in lipid and atherosclerosis pathways.Cynanchum wilfordii treatment significantly increased the body weight and decreased DAI score of UC mice(P<0.05),alleviated intestinal pathologies,and decreased JAK2 and STAT3 protein expressions in the colon tissues.Most of the 83 intersecting differential metabolites between the control,model and Cynanchum wilfordii groups were identified as glycerophospholipids,arachidonic acid,and amino acids involving glycerophospholipid metabolism and other pathways.Correlation analysis suggested that the core targets of Cynanchum wilfordii for UC participated in regulation of the metabolites.Conclusion Cynanchum wilfordii alleviates lipid and amino acid metabolism disorders to lessen UC in mice by regulating the core targets including JAK2 and STAT3 and the levels of endogenous metabolites.